The present invention is directed to intermediates and a stepwise process for the conversion of ethyl 4-chloro-3R-hydroxybutyrate, of the formula (II) below, to optically active 3-thiolanyl sulfonate esters of the formula ##STR2## wherein R is (C.sub.1 -C.sub.3)alkyl, phenyl or tolyl.
The compounds of formula (I) are particularly valuable intermediates in the preparation of certain penem antibiotics. Thus, antibacterial 5R,6S-6-(1R-hydroxyethyl)2-(cis-1-oxo-3-thiolanylthio)-2-penem-3-carboxyli c acid, which is a diastereomeric mixture of two compounds, was earlier disclosed as a valuable antibacterial substance by Hamanaka, U.S. Pat. No. 4,619,924; while Volkmann et al., in U.S. Pat. No. 4,739,047, have disclosed an alternative synthesis for that substance. More recently, the preferred diastereoisomer [5R,6S-6-(1R-hydroxyethyl)-2-(1R-oxo3S-thiolanylthio)-2-penem-3-carboxylic acid]and a process therefor, have been identified and disclosed in my International Application No. PCT/US87/01114, designating inter alia the United States of America, published on Nov. 17, 1988 as WO-88/08845. Key to synthesis of this diastereoisomer is the optically active intermediate of the formula (I), earliest prepared by the following sequence: ##STR3## More recently, in commonly assigned, copending U.S. patent application, Ser. No. 07/183,102, filed Apr. 19, 1988, Urban describes a multistep synthesis of the compound of the formula (I) from D-methionine, as follows: ##STR4## We have now discovered that the optically active compounds of the formula (I) are most conveniently and
readily prepared by a three step process from ethyl 4-chloro-3R-hydroxybutyrate, an optically active compound now easily available in 97% yield by hydrogenation of ethyl 4-chloroacetoacetate over an optically active ruthenium catalyst according to the method of Kitamura, et al., Tetrahedron Letters, vol. 29, pp. 1555-1556, 1988.
The presently prepared thiolanyl sulfonate esters of the formula (I) are used in the synthesis of the above identified diastereomeric penem antibiotic according to methods which are available to the public in my published International patent application WO-88/08845, cited above, which also teaches the advantageous utility of this penem antibiotic.